Intervention with ICOSL Antibodies Alleviates Inflammatory Infiltrations in Mice with Neutrophilic Asthma.

Background: Neutrophilic asthma is characterized by the predominant infiltration of neutrophils in airway inflammation. Objective: To explore the therapeutic potential of an antibody against the inducible T cell co-stimulator ligand (ICOSL) in a mouse model of neutrophilic asthma. Methods: Female BALB/c mice were randomly assigned to different groups. They were then injected with ovalbumin (OVA)/lipopolysaccharides (LPS) to induce neutrophilic asthma. The mice were then treated with either anti-ICOSL (the I group), control IgG (the G group), or no treatment (the N group). Additionally, a control group of mice received vehicle PBS and was labeled as the C group (n=6 per group). One day after the last allergen exposure, cytokine levels were measured in plasma and bronchoalveolar lavage fluid (BALF) using ELISA. After analyzing and categorizing BALF cells, the lung tissues were examined histologically and immunohistochemically. Results: Administering anti-ICOSL resulted in a significant decrease in the total number of inflammatory infiltrates and neutrophils found in BALF. Moreover, it led to a decrease in the levels of interleukin (IL)-6, IL-13, and IL-17 in both BALF and plasma. Additionally, there was an increase in IFN-γ levels in the BALF of asthmatic mice (p<0.05 for all). Treatment with anti-ICOSL also reduced lung interstitial inflammation, mucus secretion, and ICOSL expression in asthmatic mice. Conclusion: The treatment of anti-ICOSL effectively improved lung interstitial inflammation and mucus secretion in mice with neutrophilic asthma by restoring the balance of Th1/Th2/Th17 responses. These findings indicate that blocking the ICOS/ICOSL signaling could be an effective way to manage neutrophilic asthma.

Multiple and large simple renal cysts are associated with glomerular filtration rate decline: a cross-sectional study of Chinese population.

BACKGROUND: Although simple renal cyst (SRC) is a kind of structural alterations of kidney with age, the relationship between SRC and renal function is still obscure. We investigated the relationship between SRC and renal function in Chinese population. METHODS: The medical records of 41,842 individuals who underwent physical examinations at the Health Check-up Center at our institution in 2018 were reviewed. According to whether with SRC, they were divided into no-SRC and SRC groups. SRCs were classified into subgroups based on number (< 2 vs. ≥ 2) and size (< 2 cm vs. ≥ 2 cm). Logistic regression was used to examine the relationship between SRC and estimated glomerular filtration rate (eGFR). RESULTS: Multinomial logistic regression analysis showed that the adjusted odds ratio (OR) for eGFR slight decline in subjects with SRC was 1.26(95% confidence interval (95% CI):1.17-1.35, p < 0.001), and the OR for eGFR severe decline was 1.35(95% CI: 1.16-1.56, p < 0.001) compared with no-SRC. The adjusted OR of SRC number ≥ 2 and ≥ 2 cm on the risk of eGFR severe decline was the highest (OR:1.68, 95% CI:1.25-2.23, p < 0.01) of four SRC subgroups. CONCLUSIONS: SRC is related to eGFR decline, especially when the person with one more SRCs and the size of SRC is more than 2 cm. SRC could be a warning sign for clinicians to judge the decline of renal function.

Etiology and clinical features of infection-associated plastic bronchitis in children.

OBJECTIVE: To investigate the etiological characteristics of plastic bronchitis (PB) caused by pulmonary infections in children and to identify any differences in the clinical features of PB cases caused by different pathogens. METHOD: We collected data on children diagnosed with PB and admitted to the Respiratory Department at Soochow University Children's Hospital between July 2021 and March 2023 utilizing electronic bronchoscopy. We analyzed clinical characteristics and the species of pathogens causing the illness in these children. RESULT: A total of 45 children were enrolled. The main clinical symptoms observed were cough (100%), fever (80%), shortness of breath (28.9%), and wheezing (20.0%). Pathogens were identified in 38 (84.4%) patients. Mycoplasma pneumoniae (MP) had the highest detection rate at 53.3%, followed by the Boca virus at 26.7%. MP-induced PB typically occurs in older children with an average age of 7.46 ± 2.36 years, with the main symptoms including high fever (85.7%) and local hyporespiration (42.9%). In contrast, Boca virus-induced PB tends to occur in younger children, with the main symptoms of moderate fever (54.5%), and wheezing (54.5%). The MP group exhibited a higher incidence of both internal and external pulmonary complications, including pleural effusion (42.9%), elevated aspartate aminotransferase (52.4%), lactic dehydrogenase (76.2%), and D-D dimer (90.5%). Conversely, the Boca virus group primarily showed pulmonary imaging of atelectasis (81.8%), with no pleural effusion. The average number of bronchoscopic interventions in the MP group was 2.24 ± 0.62, which was significantly higher than that required in the Boca virus group (1.55 ± 0.52). During the second bronchoscopy, 57.1% of children in the MP group still had visible mucus plugs, while none were observed in the Boca virus group. CONCLUSION: MP and Boca virus are the primary pathogens responsible for PB among children. The clinical manifestations of PB typically vary significantly based on the pathogen causing the condition.

The predictive values of soluble B7-DC in children with refractory mycoplasma pneumoniae pneumonia.

Background: Refractory mycoplasma pneumoniae pneumonia (RMPP) is a serious mycoplasma pneumoniae infection and is difficult to diagnose early. The levels of serum soluble B7-dendritic cell (sB7-DC) in children with mycoplasma pneumoniae pneumonia (MPP) were assessed to explore the clinical significance of sB7-DC levels in RMPP. Methods: A total of 65 patients with mycoplasma pneumoniae pneumonia (MPP) were enrolled in this study between January 2017 and December 2018. The patients were divided into the general mycoplasma pneumoniae pneumonia (GMPP) (n=30) and RMPP groups (n=35); the data of 20 normal children served as a control group (n=20). An enzyme-linked immunoassay kit was used to detect the expression of soluble B7-dendritic cell (sB7-DC) and other inflammatory factors. Binary logistic regression was performed to identify the independent predictors of RMPP. Receiver operating characteristic (ROC) curves were drawn to evaluate the value of each independent risk factor in the early diagnosis of RMPP. Results: The results showed that compared to the GMPP group, children in the RMPP group had a significantly longer hospital stay and had a significantly longer fever duration (P<0.05). The values of interferon-gamma (IFN-γ), interleukin 17 (IL-17), and sB7-DC in the RMPP group were significantly higher than those in the normal control and GMPP groups (all P<0.05). The results of the correlation analysis showed that sB7-DC was positively correlated with IFN-γ and IL-17 and these indicators could be used in combination to evaluate the severity of the disease. The binary logistic regression analysis identified IL-17 and sB7-DC as independent risk factors for RMPP (P<0.05). The ROC curve analysis showed that the cut-off values of IL-17 and sB7-DC were 309.6 pg/L and 1,109.7 pg/mL, respectively. The areas under the curve (AUCs) of IL-17 and sB7-DC were 0.741 and 0.794, respectively. The sensitivity of IL-17 to RMPP prediction was 83.3%, and the specificity was 62.9%. The sensitivity and specificity of sB7-DC to RMPP were 86.7% and 62.9%, indicating that sB7-DC had the highest predictive power for RMPP. Conclusions: The level of serum sB7-DC may play an important role in the early diagnosis of RMPP. Our research results provide a theoretical basis for the early diagnosis of RMPP.

Relationship between meteorological and environmental factors and acute exacerbation for pediatric bronchial asthma: Comparative study before and after COVID-19 in Suzhou.

Objective: Climate and environmental change is a well-known factor causing bronchial asthma in children. After the outbreak of coronavirus disease (COVID-19), climate and environmental changes have occurred. The present study investigated the relationship between climate changes (meteorological and environmental factors) and the number of hospitalizations for pediatric bronchial asthma in Suzhou before and after the COVID-19 pandemic. Methods: From 2017 to 2021, data on daily inpatients diagnosed with bronchial asthma at Children's Hospital of Soochow University were collected. Suzhou Meteorological and Environmental Protection Bureau provided daily meteorological and environmental data. To assess the relationship between bronchial asthma-related hospitalizations and meteorological and environmental factors, partial correlation and multiple stepwise regression analyses were used. To estimate the effects of meteorological and environmental variables on the development of bronchial asthma in children, the autoregressive integrated moving average (ARIMA) model was used. Results: After the COVID-19 outbreak, both the rate of acute exacerbation of bronchial asthma and the infection rate of pathogenic respiratory syncytial virus decreased, whereas the proportion of school-aged children and the infection rate of human rhinovirus increased. After the pandemic, the incidence of an acute asthma attack was negatively correlated with monthly mean temperature and positively correlated with PM2.5. Stepwise regression analysis showed that monthly mean temperature and O3 were independent covariates (risk factors) for the rate of acute asthma exacerbations. The ARIMA (1, 0, 0) (0, 0, 0) 12 model can be used to predict temperature changes associated with bronchial asthma. Conclusion: Meteorological and environmental factors are related to bronchial asthma development in children. The influence of meteorological and environmental factors on bronchial asthma may be helpful in predicting the incidence and attack rates.

Crown Ether-Based Ion Transporters in Bilayer Membranes.

Bilayer membranes that enhance the stability of the cell are essential for cell survival, separating and protecting the interior of the cell from its external environment. Membrane-based channel proteins are crucial for sustaining cellular activities. However, dysfunction of these proteins would induce serial channelopathies, which could be substituted by artificial ion channel analogs. Crown ethers (CEs) are widely studied in the area of artificial ion channels owing to their intrinsic host-guest interaction with different kinds of organic and inorganic ions. Other advantages such as lower price, chemical stability, and easier modification also make CE a research hotspot in the field of synthetic transmembrane nanopores. And numerous CEs-based membrane-active synthetic ion channels were designed and fabricated in the past decades. Herein, the recent progress of CEs-based synthetic ion transporters has been comprehensively summarized in this review, including their design principles, functional mechanisms, controllable properties, and biomedical applications. Furthermore, this review has been concluded by discussing the future opportunities and challenges facing this research field. It is anticipated that this review could offer some inspiration for the future fabrication of novel CEs-derived ion transporters with more advanced structures, properties, and practical applications.

[Association of Haemophilus influenzae infection with environmental and climatic factors in Suzhou, China]. / è‹å·žåœ°åŒºæµæ„Ÿå—œè¡€æ†èŒæ„ŸæŸ“ä¸ŽçŽ¯å¢ƒæ°”å€™çš„ç›¸å ³å› ç´ åˆ†æž.

OBJECTIVES: To investigate the epidemiological characteristics of respiratory Haemophilus influenzae (HI) infection in children in Suzhou, China and its association with climatic factors and air pollutants. METHODS: The data on air pollutants and climatic factors in Suzhou from January 2016 to December 2019 were collected. Respiratory secretions were collected from 7 940 children with acute respiratory infection who were hospitalized during this period, and bacterial culture results were analyzed for the detection of HI. A stepwise regression analysis was used to investigate the association of HI detection rate with air pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) and climatic factors (monthly mean temperature, monthly mean humidity, monthly total rainfall, monthly total sunshine duration, and monthly mean wind speed). RESULTS: In 2016-2019, the 4-year overall detection rate of HI was 9.26% (735/7 940) among the children in Suzhou. The children aged <1 year and 1-<3 years had a significantly higher HI detection rate than those aged ≥3 years (P<0.01). The detection rate of HI in spring was significantly higher than that in the other three seasons, and the detection rate of HI in autumn was significantly lower than that in the other three seasons (P<0.001). The multiple linear regression analysis showed that PM10 and monthly mean wind speed were independent risk factors for the detection rate of HI: the detection rate of HI was increased by 0.86% for every 10 µg/m3 increase in the concentration of PM10 and was increased by 5.64% for every 1 m/s increase in monthly mean wind speed. Air pollutants and climatic factors had a lag effect on the detection rate of HI. CONCLUSIONS: HI is an important pathogen for acute respiratory infection in children in Suzhou and is prevalent in spring. PM10 and monthly mean wind speed are independent risk factors for the detection rate of HI.

The CARDS toxin of Mycoplasma pneumoniae induces a positive feedback loop of type 1 immune response.

Background: Within the past 3-5 years, Mycoplasma pneumoniae has become a major pathogen of community-acquired pneumonia in children. The pathogenic mechanisms involved in M. pneumoniae infection have not been fully elucidated. Methods: Previous protein microarray studies have shown a differential expression of CXCL9 after M. pneumoniae infection. Here, we conducted a hospital-based study to explore the clinical significance of the type 1 immune response inflammatory factors interferon (IFN)-γ and CXCL9 in patients with M. pneumoniae pneumonia (MPP). Then, through in vitro experiments, we explored whether CARDS toxin stimulated F-DCs (dendritic cells incubated with Flt3L) to promote Th-cell differentiation; we also investigated the IFN-γ-induced CXCL9 secretion pathway in macrophages and the role of CXCL9 in promoting Th1 cell migration. Results: The CXCL9 expression level was upregulated among patients with a higher fever peak, fever duration of greater than 7 days, an imaging manifestation of lobar or segmental, or combined pleural effusion (P<0.05). The peripheral blood levels of IFN-γ and CXCL9, which were higher in patients than in the healthy control group, were positively correlated with each other (r=0.502, P<0.05). In patients, the CXCL9 expression level was significantly higher in the bronchoalveolar lavage fluid (BALF) than in the peripheral blood, and the BALF CXCL9 expression level was higher than that in the healthy control group (all P<0.05). Our flow cytometry analysis revealed that M1-phenotype macrophages (CD16 + CD64 + CD163-) were predominant in the BALF from children with MPP. In in vitro experiments, F-DCs stimulated with CARDS toxin promoted the differentiation of CD4 + IFN-γ + Th (Th1) cells (P<0.05). Moreover, IFN-γ induced high levels of CXCL9 expression in M1-type macrophages in a dose-dependent and time-dependent manner. Additionally, macrophages transfection with STAT1-siRNA-1 downregulated the expression of CXCL9 (P<0.05), and CXCL9 promoted Th1 cell migration (P<0.05). Conclusions: Our findings suggest that CARDS toxin induces a type 1 immune response positive feedback loop during M. pneumoniae infection; this putative mechanism may be useful in future investigations of immune intervention approaches for M. pneumoniae pneumonia.

MiR-493-5p inhibits Th9 cell differentiation in allergic asthma by targeting FOXO1.

The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.

Graphene functionalized with structurally complementary amino acids for sensitive recognition of N-linked glycopeptides.

Herein, a hydrophilic graphene composite functionalized with glutathione (GSH) and L(+)-Cysteine (Cys) was prepared via a simple and fast synthesis route, which was named G@S@Au@GC. The combination attack with two different zwitterionic polymers resulted in enhanced adsorption sites for glycopeptides. The obtained G@S@Au@GC exhibited excellent performance on a low limit of detection (0.2 fmol), a high selectivity (HRP: bovine serum albumin = 1:1500), a good load capacity (250 µg•mg-1) and recovery rate (93%), which was also evaluated with IgG. Subsequently, 60 glycopeptides from complex biological sample (human saliva) were identified by Nano-LC-MS/MS. The advantages of combination attack, low-cost, simple and fast synthesis, and superior enrichment performance make G@S@Au@GC composite a bright future on glycoproteomics analysis and related diseases.

LncRNATUG1 Facilitates Th2 Cell Differentiation by Targeting the miR-29c/B7-H3 Axis on Macrophages.

The role of long non-coding RNAs (lncRNA) in asthma remains unclear. In this study, we examined the role of long non-coding RNA taurine upregulated 1 (lncRNA TUG1) in asthma. We found that lncRNA TUG1 is one of the differentially expressed lncRNAs in the monocytes of asthmatic children and is associated with Th cell differentiation. LncRNA TUG1 and miR-29c are mainly distributed in the cytoplasm of macrophages. Our data suggested that lncRNA TUG1 increased in macrophages stimulated by House Dust Mite in a dose-dependent manner. Using loss- and gain of function strategy, we found that miR-29c might regulate Th2 cell differentiation by directly targeting co-stimulatory molecule B7-H3. Furthermore, down-regulation of lncRNA TUG1 decreased the level of GATA3 in CD4+T cells and was associated with miR-29c/B7-H3 axis. Moreover, the dual-luciferase reporter assay confirmed that lncRNA TUG1 serves as a competing endogenous RNA to sponge miR-29c. According to the rescue experiment, lncRNA TUG1 regulated Th2 cell differentiation via miR-29c. These data suggest that lncRNA TUG1 in macrophages regulates Th2 cell differentiation via miR-29c/B7-H3 axis.

Differences of clinical features and prognosis between Mycoplasma pneumoniae necrotizing pneumonia and non-Mycoplasma pneumoniae necrotizing pneumonia in children.

BACKGROUND: In the past few years, Mycoplasma pneumoniae (Shi et al. Lancet 390:946-958, 2017) infection has been reported more in China. However, there are few studies on the clinical characteristics and prognosis of necrotizing pneumonia (NP) (Griffiths et al. Nature 583:615-619, 2020) caused by different pathogens. METHODS: A retrospective analysis was performed, including 31 children with a clinical diagnosis of NP in the hospital from January 1, 2013 to January 31, 2020. A total of 11 children with MPNP were included in the observation group and the other 20 children with other pathogens were included in the control group. The clinical manifestations, laboratory data, imaging findings, treatments and outcomes were analyzed. RESULTS: The proportion of dyspnea cases was significantly higher in the non-Mycoplasma pneumoniae necrotizing pneumonia (N-MPNP) group than that in the Mycoplasma pneumoniae necrotizing pneumonia (MPNP) group (P = 0.02).The LDH level of all patients in the MPNP group was higher than the normal value, with a median value of 805.0 U/L, which was significantly higher than those in the N-MPNP group (414.0 [299.9-540.6] U/L; Z = - 2.518; P = 0.012). The white blood cells (WBCs) count of the N-MPNP group was 17.8 (11.1-21.7) × 109/L, which was significantly higher than that of the MPNP group (10.2 [6.3-14.1] × 109/L; P < 0.05). The mean time of pulmonary necrosis in the MPNP group was 20.9 ± 6.9 days, which was higher than that of the N-MPNP group (16.8 ± 6.1 days; t = 3.101; P = 0.004). The incidence of pleural effusion in the N-MPNP group (19 patients, 95%) was significantly higher than that in the MPNP group (six patients, 54.55%) (P = 0.013). Among them, two patients received bronchoscopy lavage at a maximum four times, and the cases of plastic bronchitis were seen only in the MPNP group (3 cases; P = 0.037).The length of stay was 18 (10-22) days in the MPNP group and 23.5 (13.5-47) days in the N-MPNP group and no significant difference was observed between the two groups (Z = - 1.923, P = - 0.055). CONCLUSIONS: 1. MP infection is the most common infection in children with NP in the Suzhou area. There is no gender and age difference between MPNP and N-MPNP, but the bacterial infection was mainly observed in the N-MPNP group. 2. Children in the N-MPNP group have more severe clinical symptoms, were more prone to shortness of breath, had a longer hospital stay, and had earlier imaging manifestations of necrosis, whereas children in the MPNP group were more likely to have plastic bronchitis. The level of WBC and LDH and the nature of pleural effusion can be used to identify MPNP and N-MPNP to some extent. 3. The prognosis of MPNP was better than that of N-MPNP. There were no death cases. Pleural thickening, pulmonary fibrosis, and bronchiectasis were the most common sequelae. Compared with N-MPNP, the recovery time of lung imaging in MPNP was shorter.

Post-synthesis of biomimetic chitosan with honeycomb-like structure for sensitive recognition of phosphorylated peptides.

Chemical modification of biological materials is indispensable for enrichment of phosphorylated peptides. In this work, we synthesized a biomimetic honeycombed affinity chromatography (IMAC) adsorbent by preparing Crosslinked Chitosan, chelating aminomethyl phosphate decorated with Ti (IV) cation. The as-prepared CTSM@AMPA-Ti4+ composites with stable structure, low steric hindrance, and high Ti4+ loading amount were used as a promising adsorbent for enrichment of phosphopeptides. CTSM@AMPA-Ti4+ showed extremely high sensitivity (0.4 fmol) and selectivity at a low composition molar ratio of ß-casein/BSA (1:1000). What's more, it can keep its performance in the case that used to capture phosphorylated peptides from standard protein ten times or soaking in the acid/base solution for a long time. In addition, CTSM@AMPA-Ti4+ successfully captured 35 phosphorylated peptides from human saliva. This study offers a way about diversiform functionalization of CTSM in phosphoproteome analysis and disease research.

Gold nanoparticle-glutathione functionalized MOFs as hydrophilic materials for the selective enrichment of glycopeptides.

Herein, a novel zwitterionic hydrophilic metal-organic framework (MOF)-functionalized material was synthesized through grafting l-glutathione (GSH) onto the Au which acts as the intermediate layer to modify the base material (PEI-ZIF-8) by the sulfhydryl group provided by GSH and the affinity provided by Au (denoted as PEI-ZIF-8@Au@GSH). The obtained product was employed to capture glycopeptides. Benefit from its excellent hydrophilic properties, abundant amphoteric ions, and unique large specific surface area, this material demonstrated amazing ability in the enrichment and identification of glycopeptides. As a result, the PEI-ZIF-8@Au@GSH displayed high sensitivity (as low as 2 fmol), excellent binding capacity (500 mg/g), outstanding enrichment selectivity (maximum mass ratio HRP to BSA is 1:1000) toward glycopeptides, and the ability to recycle at least five times. Furthermore, 35 and 51 glycopeptides were successfully detected from 5 µL human saliva and human serum respectively in the examination of the actual sample by MALDI-TOF MS. The above results indicated that the PEI-ZIF-8@Au@GSH had a satisfactory potential in the field of glycoproteomics.

Wogonoside promotes apoptosis and ER stress in human gastric cancer cells by regulating the IRE1α pathway.

Gastric cancer is a disease that occurs in the digestive system of humans and remains a problem in the medical field. Wogonoside, a natural flavonoid, has been reported to exert antitumor effects on various types of tumors. However, the effects of wogonoside on gastric cancer remain elusive. The aim of the present study was to detect whether wogonoside treatment could induce apoptosis and ER stress in gastric cancer cells. In the present study, CCK-8 assay was used to detect the cell viability, Annexin V/PI staining was used to detect the cells apoptosis, western blot analysis and real-time PCR analysis was used to detect the endoplasmic reticulum (ER) stress in the AGS and MKN-45 gastric cancer cell lines. Wogonoside treatment reduced the viability of AGS and MKN-45 cells and induced apoptosis. Furthermore, the expression level of caspase-3 and -9 significantly increased following wogonoside treatment compared with that in non-treated cells, and the protein expression levels of proapoptotic Bax and antiapoptotic Bcl-2 increased and decreased, respectively compared with that in the control group. In addition, the phosphorylated protein expression levels of mitogen-activated protein kinase kinase 5 (ASK1) and JNK increased following wogonoside treatment, and the protein expression levels of tumor necrosis factor receptor-associated factor 2 (TRAF2) and serine/threonine-protein kinase/endoribonuclease IRE1 (IRE1α) were also increased following treatment with 50 µM wogonoside for 48 h. Furthermore, the interactions between IRE1α, TRAF2 and ASK1 significantly increased following wogonoside treatment, suggesting that wogonoside induced endoplasmic reticulum (ER) stress in the AGS and MKN-45 cell lines. In addition, small interfering RNA-mediated silencing of IRE1α suppressed the activity of the IRE1α-TRAF2-ASK1 complex and prevented wogonoside-induced cell apoptosis. In conclusion, the results of the present study suggested that wogonoside exhibited antitumor activity by inducing ER stress-associated cell death through the IRE1α-TRAF2-ASK1 pathway.

Risk factors for recurrent wheezing after bronchiolitis in infants: 2-year follow up in China.

BACKGROUND: Infants with bronchiolitis have an increased risk of developing recurrent wheezing and asthma. However, the risk factors for the development of recurrent wheezing after bronchiolitis remains controversial. Our study was to investigate risk factors of post-bronchiolitis recurrent wheezing. METHODS: Infants with bronchiolitis were enrolled from November 2016 through March 2017. Nasopharyngeal aspirates were obtained for detection of respiratory viruses which were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and direct immunofluorescent assay. Serum cytokines including TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α were measured by flow cytometry. Patients were followed up every 3 months for a duration of 2 years by telephone or at outpatient appointments. RESULTS: We enrolled 89 infants, of which 81 patients were successfully followed up. In total, 22.2% of patients experienced recurrent wheezing episodes. The proportion of patients with history of eczema, systemic glucocorticoid use and patients with moderate-to-severe disease were significantly higher in the recurrent wheezing group than the non-recurrent wheezing group (83.3% vs 52.4%; 66.7% vs 36.5%; 61.1% vs 33.3%, respectively, all P < 0.05); There were no significant differences between patients with and without recurrent wheezing episodes in the levels of TSLP, IL2, IL13, TIMP-1, MMP-9, IL33, IL5, IL4, IL25, TNF- α and MIP-1α (P > 0.05). Logistic regression analysis showed that history of eczema was an independent risk factor for post-bronchiolitis recurrent wheezing (odds ratio [OR] = 5.622; 95% confidence interval [CI], 1.3-24.9; P = 0.023). CONCLUSION: The incidence of recurrent wheezing among infants after contracting bronchiolitis was 22.2% during a 2-year follow-up. History of eczema was the only independent risk factor identified and no correlation was found between the specific virus and disease severity in children with post-bronchiolitis recurrent wheezing.

Hydrophilic carrageenan functionalized magnetic carbon-based framework linked by silane coupling agent for the enrichment of N-glycopeptides from human saliva.

In this work, a magnetic graphene material coated with mesoporous silica was selected as the substrate, 3-glycidoxypropyltrimethoxysilane and polyethyleneimine were sequentially bonded through chemical reactions, and then carrageenan was successfully introduced by electrostatic interaction; finally, hydrophilic nanocomposite material was prepared. Due to the large number of hydrophilic groups, and polyethyleneimine was connected by means of chemical bonds, this material exhibits good hydrophilicity and stability for glycopeptide enrichment. In the actual enrichment process, nanomaterial exhibits high selectivity (1:500), high sensitivity (2 fmol), and good repeatability (five cycles). In addition, the synthesized material also shows a good enrichment effect in the face of actual complex biological samples, which captured 40 N-glycopeptides from human saliva, indicating the application potential for enrichment of N-glycopeptides.

Clinical Characteristics of Pediatric Respiratory Tract Infection and Respiratory Pathogen Isolation During the Coronavirus Disease 2019 Pandemic.

Objective: We sought to compare the clinical characteristics of pediatric respiratory tract infection and respiratory pathogen isolations during the coronavirus disease (COVID-19) pandemic to those of cases in 2018 and 2019. Methods: Our study included all children from 28 days to 15 years old with respiratory tract infections who were admitted to the Department of Respiration, in the Children's Hospital of Soochow University, between January 2018 and December 2020. Human rhinovirus (HRV) and human metapneumovirus (hMPV) were detected by reverse transcription polymerase chain reaction (RT-PCR). Mycoplasma pneumoniae (MP) and human bocavirus (HBoV) were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR); In parallel, Mycoplasma pneumoniae was detected by enzyme-linked immunosorbent assays, and bacteria were detected by culture in blood, bronchoalveolar lavage specimen, and pleural fluid. Results: Compared to 2018 and 2019, the pathogen detection rate was significantly lower in 2020. With regard to infections caused by single pathogens, in 2020, the detection rates of MP were the lowest and those of HRV were the highest when compared to those in 2018 and 2019. Meanwhile, the positive rates of respiratory syncytial virus (RSV) and hMPV reported in 2020 were less than those recorded in 2018 but similar to those recorded in 2019. Also, the 2020 rate of adenovirus (ADV) was lower than that recorded in 2019, but similar to that recorded in 2018. There were no statistical differences in the positive rates of HBoV and PIV III over the 3 years surveyed. Infections in infants were significantly less common in 2020, but no significant difference was found among children aged 1 to 3 years. The detection rate of pathogens in children old than 5 years in 2020 was significantly lower than those recorded in the previous 2 years. Notably, the pathogen detection rates in the first and second quarters of 2020 were similar to those recorded in the previous 2 years; however, the rates were reduced in the third and fourth quarters of 2020. As for co-infections, the positive rate was at its lowest in 2020. In the previous 2 years, viral-MP was the most common type of mixed infection. By contrast, in 2020, viral-viral infections were the most common combination. Conclusion: The pathogen detection rate was significantly reduced in Suzhou City during the COVID-19 pandemic. Public interventions may help to prevent respiratory pathogen infections in children.

The expression and function of programmed death-ligand 1 and related cytokines in neutrophilic asthma.

BACKGROUND: Programmed death-ligand 1 (PD-L1) is an important immune checkpoint inhibitor. Recent studies suggest that the PD-L1-mediated pathway may be a promising target in allergic asthma. However, the mechanism by which PD-L1 represses neutrophilic asthma (NA) remains unclear. In this study, we examined correlations between the expression of PD-L1 and the production of T helper cell type 1 (Th1), T helper cell type 2 (Th2), and T helper cell type 17 (Th17) cells in pediatric patients with NA and a mouse model. METHODS: The clinical samples of 26 children with asthma and 15 children with a bronchial foreign body were collected over a period of 12 months by the Children's Hospital of Soochow University. An experimental mouse model of asthma was established to study NA. An enzyme-linked immunoassay (ELISA) was used to assess soluble PD-L1 (sPD-L1) and cytokines [e.g., interleukin (IL)-4, IL-6, interferon gamma (IFN-γ), IL-17 and granulocyte-macrophage colony-stimulating factor (GM-CSF)] in bronchoalveolar lavage fluid (BALF). RESULTS: NA patients had significantly higher levels of sPD-L1, IL-6, IL-17, and GM-CSF in their BALF than non-NA and control patients (P<0.05). In a murine model of asthma, the positive rate and fluorescence intensity of PD-L1 in the NA group and the immunoglobulin G (IgG)-treated NA group were higher than in the PD-L1 antibody (Ab)-treated NA group and the phosphate-buffered saline (PBS) control group (P<0.05). In the plasma and the BALF of the NA group and the IgG-treatment NA group, the levels of IL-17, IL-4, tumor necrosis factor alpha (TNF-α), and granulocyte colony-stimulating were higher than those in the PBS control group (P<0.05). The histopathological examination of lung tissues from all mice groups showed that a large number of inflammatory cells were found around the airway in the NA group and the IgG-treatment group. CONCLUSIONS: PD-L1 may contribute to the Th17/IL-17 immune response, which is associated with neutrophilic inflammation and asthma. A PD-L1 blockade reduces pulmonary neutrophils and mucus production.

Viral etiology and atopic characteristics in high-risk asthmatic children hospitalized for lower respiratory tract infection.

BACKGROUND: Viral etiology and atopic characteristics, e.g., allergens and fractional exhaled nitric oxide (FeNO), play essential roles in asthma development. This study aimed to investigate associations among them in children at high risk of developing asthma to guide reliable diagnosis and treatment of wheezing. METHODS: From April 2016 to August 2017, 135 children aged <3 years identified as being at high risk of asthma and hospitalized for lower respiratory tract infection (LRTI) with wheezing were recruited as research subjects (observation group). Real-time fluorescent polymerase chain reaction (PCR) was used to explore their etiology. Samples were also evaluated with Phadiatop (Pharmacia Diagnostics AB, Uppsala, Sweden). Additionally, 200 non-asthmatic, non-allergic, healthy children who were screened and followed up in the Echocardiography clinic during the study period were recruited as a healthy control group for FeNO measurement, and the observation group also underwent FeNO measurement. RESULTS: Among the observation group, viruses were positively detected in 49.63%. The most often detected virus was human rhinovirus (HRV; 25.19%). Compared with children aged <12 months, those aged 1-3 years were more susceptible to HRV infection and had lower sensitivity rates for inhalant allergens and higher T-IgE. The virus-detected group had a higher sensitivity rate for inhalant allergens compared with the virus-undetected group. FeNO in the observation group was lower than that in the healthy control group. The second-wheezing group had higher sensitivity rates for dust mites and fungi and higher T-IgE levels compared with the first-wheezing group. CONCLUSIONS: HRV was the most common viral pathogen present during an asthmatic attack in infants and young children at elevated risk of asthma. Allergy is a risk factor for both initial wheezing and repeated wheezing. Inhalant allergen-sensitive children are more susceptible than others to viral infection.